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BackgroundMetastatic relapse of prostate cancer after radiotherapy is a significant cause of prostate cancer-related morbidity and mortality. PLOD2 is a mediator of invasion and metastasis that we identified as being upregulated in our highly aggressive radiorecurrent prostate cancer cell line.MethodsPatient dataset analysis was conducted using a variety of prostate cancer cohorts. Prostate cancer cell lines were treated with siRNA, or the drug PX-478 prior to in vitro invasion, migration, or in vivo chick embryo (CAM) extravasation assay. Protein levels were detected by western blot. For RNA analysis, RNA sequencing was conducted on PLOD2 knockdown cells and validated by qRT-PCR.ResultsPLOD2 is a negative prognostic factor associated with biochemical relapse, driving invasion, migration, and extravasation in radiorecurrent prostate cancer. Mechanistically, HIF1α upregulation drives PLOD2 expression in our radiorecurrent prostate cancer cells, which is effectively inhibited by HIF1α inhibitor PX-478 to reduce invasion, migration, and extravasation. Finally, the long non-coding RNA LNCSRLR acts as a promoter of invasion downstream of PLOD2.ConclusionsTogether, our results demonstrate for the first time the role of PLOD2 in radiorecurrent prostate cancer invasiveness, and point towards its potential as a therapeutic target to reduce metastasis and improve survival outcomes in prostate cancer patients.

To model the problem of radiation resistance in prostate cancer, cell lines mimicking a clinical course of conventionally fractionated or hypofractionated radiotherapy have been generated. Proteomic analysis of radiation resistant and radiosensitive DU145 prostate cancer cells detected 4410 proteins. Over 400 proteins were differentially expressed across both radiation resistant cell lines and pathway analysis revealed enrichment in epithelial to mesenchymal transition, glycolysis and hypoxia. From the radiation resistant protein candidates, the cell surface protein CD44 was identified in the glycolysis and epithelial to mesenchymal transition pathways and may serve as a potential therapeutic target.

BackgroundWhile prostate cancer can often manifest as an indolent disease, the development of locally-advanced or metastatic disease can cause significant morbidity or mortality. Elucidation of molecular mechanisms contributing to disease progression is crucial for more accurate prognostication and effective treatments. R-Spondin 3 (RSPO3) is a protein previously implicated in the progression of colorectal and lung cancers. However, a role for RSPO3 in prostate cancer prognosis and behaviour has not been explored.MethodsWe compare the relative levels of RSPO3 expression between normal prostate tissue and prostate cancer in two independent patient cohorts (Taylor and GSE70768-Cambridge). We also examine the association of biochemical relapse with RSPO3 levels in these cohorts. For elucidation of the biological effect of RSPO3, we use siRNA technology to reduce the levels of RSPO3 in established prostate cancer cell lines, and perform in vitro proliferation, invasion, western blotting for EMT markers and clonogenic survival assays for radiation resistance. Furthermore, we show consequences of RSPO3 knockdown in an established chick chorioallantoic membrane (CAM) assay model of metastasis.ResultsRSPO3 levels are lower in prostate cancer than normal prostate, with a tendency for further loss in metastatic disease. Patients with lower RSPO3 expression have lower rates of biochemical relapse-free survival. SiRNA-mediated loss of RSPO3 results in no change to clonogenic survival and a lower proliferative rate, but increased invasiveness in vitro with induction of epithelial-mesenchymal transition (EMT) markers. Consistent with these results, lower RSPO3 expression translates to greater metastatic capacity in the CAM assay. Together, our preclinical findings identify a role of RSPO3 downregulation in prostate cancer invasiveness, and provide a potential explanation for how RSPO3 functions as a positive prognostic marker in prostate cancer.

MicroRNAs are small non‑coding RNA molecules which act as modulators of gene function, and have been identified as playing important roles in cancer as both tumor suppressors and oncogenes. The present study aimed to examine the role of miR‑198 in prostate cancer aggression by analyzing how it influences several hallmarks of cancer. Abundance of miR‑198 in prostate cancer and association with clinical characteristics was analyzed using a CPC‑Gene prostate cancer dataset. Overexpression of miR‑198 was performed using transient transfection of miR‑198 mimic prior to assaying proliferation, cell cycle, and colony formation in LNCaP and DU145 cell lines using standard protocols. In vivo tumor formation in athymic nude mice was examined using LNCaP xenografts with stable overexpression conferred using lentiviral miR‑198 transduction. Protein and mRNA abundance of MIB1 was determined using western blotting and RT‑qPCR respectively, while miR‑198 binding to MIB1 was validated using a luciferase reporter assay. miR‑198 abundance was lower in high Gleason grade prostate cancer relative to intermediate and low‑grade cancer. Overexpression of miR‑198 diminished proliferation of prostate cancer cell lines, increased G0/G1 cell cycle arrest, and significantly impaired colony formation. Elevated miR‑198 abundance was also demonstrated to impair tumor formation in vivo using LNCaP xenografts. Mindbomb E3 ubiquitin protein ligase 1 (MIB1) was demonstrated to be directly targeted by miR‑198, and knockdown of MIB1 recapitulated the effects of miR‑198 on proliferation and colony formation. The present evidence supports miR‑198 as an important tumor suppressor in prostate cancer, and demonstrates for the first time that it acts by targeting MIB1. The present study reinforces the importance and complexity of miRNA in regulating prostate cancer aggression.

Exploring high-efficiency broadband green phosphors that match the eye's natural perception to produce light-emitting diodes (LEDs) with vivid color reproduction and exceptional saturated colors is highly desired. Herein, bright green luminescence is revealed in an all-inorganic single-phase Ce3+-activated broadband garnet-type BaY2Sc2Al2SiO12 (BYSASO:Ce3+) phosphor. Under 439 nm InGaN-based blue LED chip irradiation, the representative BYSASO:3%Ce3+ sample shows a suitable green emission with the maximum emission peak position located at 532 nm and an impressive full width at half-maximum (FWHM) of 125 nm, which can cover more cyan gap without sacrificing the green components. High internal quantum efficiency (IQE = 80.1%), outstanding thermal resistance behavior (73.9%@423 K) and color stability, and appropriate CIE color coordinates of (0.3700, 0.5394) make this excellent optical material suitable for industrial application. Finally, a prototype warm white LED device is obtained with the proposed green-emitting BYSASO:3%Ce3+ phosphor and a commercial red-emitting (Ca,Sr)AlSiN3:Eu2+ phosphor upon blue chip excitation, exhibiting extraordinary optical properties with a satisfactory Ra of 93.3 and comfortable CCT of 3958 K, as well as an excellent luminous efficacy of 105.3 lm W−1. The results indicate that the green-emitting BYSASO:Ce3+ garnet phosphor has remarkable potential to serve as a conversion material for high-quality illumination. [ABSTRACT FROM AUTHOR]

In order to understand the enhancement mechanism of the interaction between functionalised carbon nanotubes and polymer matrix, and to investigate the effects of different functionalised carbon nanotubes on the properties of composites at the microscopic level, the models of pure polyurethane (PUR), carbon nanotubes/polyurethane (CNTs/PUR), hydroxyl-functionalised carbon nanotubes/polyurethane (CNTOH/PUR), and carboxyl-functionalised carbon nanotubes/polyurethane (CNTCOOH/PUR) systems were constructed, and molecular dynamics methods were used to simulate the effects of different functionalised carbon nanotubes on the mechanical properties of polyurethane composite systems. The effects of different functionalised carbon nanotubes on the properties of PUR composite systems were compared by analysing the properties of PUR and its composite systems in terms of free volume fraction (FFV), radial distribution function (RDF), binding energy, and density distribution of PUR around different functionalised carbon nanotubes. The effects of intermolecular interactions on the properties of the composite systems were elucidated at the microscopic level. The final simulation results show that the CNTCOOH/PUR composite system with added carboxylated CNTs has the highest tensile yield strength, compressive properties and modulus; the smallest free volume fraction; the strongest bonding energy between CNTCOOH and PUR matrix, the largest density distribution of PUR matrix around CNTCOOH, and the best interfacial interaction. [ABSTRACT FROM AUTHOR]